title: Translation of pre-spliced RNAs in the nuclear compartment generates peptides for the MHC class I pathway.
abstract: The scanning of maturing mRNAs by ribosomes plays a key role in the mRNA quality control process. When ribosomes first engage with the newly synthesized mRNA, and if peptides are produced, is unclear, however. Here we show that ribosomal scanning of prespliced mRNAs occurs in the nuclear compartment, and that this event produces peptide substrates for the MHC class I pathway. Inserting antigenic peptide sequences in introns that are spliced out before the mRNAs exit the nuclear compartment results in an equal amount of antigenic peptide products as when the peptides are encoded from the main open reading frame (ORF). Taken together with the detection of intron-encoded nascent peptides and RPS6/RPL7-carrying complexes in the perinucleolar compartment, these results show that peptides are produced by a translation event occurring before mRNA splicing. This suggests that ribosomes occupy and scan mRNAs early in the mRNA maturation process, and suggests a physiological role for nuclear mRNA translation, and also helps explain how the immune system tolerates peptides derived from tissue-specific mRNA splice variants.
authors.affiliation: Cibles Thérapeutiques, Equipe Labellisé la Ligue Contre le Cancer, Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche 940, Institut de Génétique Moléculaire, Hôpital St. Louis, Université Paris 7, F-75010 Paris, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Apcher
authors.forename: Guy
authors.initials: G
authors.lastname: Millot
authors.forename: Chrysoula
authors.initials: C
authors.lastname: Daskalogianni
authors.forename: Alexander
authors.initials: A
authors.lastname: Scherl
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Manoury
authors.forename: Robin
authors.initials: R
authors.lastname: Fåhraeus
mesh_terms: D002460:Cell Line; D002467:Cell Nucleus / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D013058:Mass Spectrometry; D010455:Peptides / Q000276:immunology* / Q000378:metabolism; D014176:Protein Biosynthesis / Q000276:immunology*; D012333:RNA, Messenger / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012270:Ribosomes / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*
chemical_list: D015395:Histocompatibility Antigens Class I; D010455:Peptides; D012333:RNA, Messenger
keywords: MHC class I restricted antigen presentation; mRNA maturation; nuclear translation